The patterns of codon usage between chordatesand arthropods are different but co-evolving withmutational biases

Abstract

Different frequencies amongst codons that encode the same amino acid (i.e. synonymous codons) have been observed in multiple species. Studies focused on uncovering the forces that drive such codon usage showed that a combined effect of mutational biases and translational selection works to produce different frequencies of synonymous codons. However, only few have been able to measure and distinguish between these forces that may leave similar traces on the coding regions. Here, we have developed a codon model that allows the disentangling of mutation, selection on amino acids and synonymous codons, and GC-biased gene conversion (gBGC) which we employed on an extensive dataset of 415 chordates and 191 arthropods. We found that chordates need 15 more synonymous codon categories than arthropods to explain the empirical codon frequencies, which suggests that the extent of codon usage can vary greatly between animal phyla. Moreover, methylation at CpG sites seems to partially explain these patterns of codon usage in chordates but not in arthropods. Despite the differences between the two phyla, our findings demonstrate that in both, GC-rich codons are disfavoured when mutations are GC-biased, and the opposite is true when mutations are AT-biased. This indicates that selection on the genomic coding regions might act primarily to stabilise its GC/AT content on a genome-wide level. Our study shows that the degree of synonymous codon usage varies considerably among animals, but is likely governed by a common underlying dynamic. Significance statementThe reasons for the differential usage of codons encoding for the same amino acid has puzzled scientist for decades. By examining the frequencies of synonymous codons in different species, this study presents a novel model that sheds light on the underlying factors that drive differences in codon usage between chordates and arthropods. Our analysis unveiled more extensive codon usage patterns in chordates compared to arthropods. Despite differences between the phyla, the study highlights that genome- wide selection acts to balance mutational biases, as GC-rich codons are less favoured under GC-biased mutations, while the opposite holds true for AT-biased mutations. This research provides valuable insights into our understanding of the complex interplay between mutational biases and selection forces in shaping the variation at the synonymous sites, and has important implications for future studies of genome evolution and adaptation.